Cell‐Penetrating and Neurotargeting Dendritic siRNA Nanostructures

We report the development of dendritic siRNA nanostructures that are able to penetrate even difficult to transfect cells such as neurons with the help of a special receptor ligand. The nanoparticles elicit strong siRNA responses, despite the dendritic structure. An siRNA dendrimer directed against the crucial rabies virus (RABV) nucleoprotein (N protein) and phosphoprotein (P protein) allowed the suppression of the virus titer in neurons below the detection limit. The cell‐penetrating siRNA dendrimers, which were assembled using click chemistry, open up new avenues toward finding novel molecules able to cure this deadly disease.     

A Meshless Boundary Method for Computation of Stokes Flow with Particles in the Semicircular Canals of the Inner Ear

Benign paroxismal positional vertigo (BPPV) is modeled by introducing free-floating particles (canaliths) which settle inside the semicircular canals (SCC). The Stokes flow induced by a canalith is evaluated by coupling the force coupling method (FCM) to the method of fundamental solutions (MFS). The proposed methodology results in a straightforward meshless boundary method for the simulation of bounded Stokes flow with finite-size particles. (© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Island formation and manipulation of prochiral azobenzene derivatives on Au(111)

Based on previous work with very similar azobenzene derivatives, this study of para-TBA (2,2',5,5'-tetra-tert-butylazobenzene) molecules aims to identify single intact molecules and investigate their adsorption behavior on a Au(111) surface. The molecules are found to be mobile on the surface at the deposition temperature, leading to highly ordered and enantiomerically pure molecular islands. Voltage pulses between the surface and the tip of a scanning tunneling microscope are used to change the chirality of the adsorbate molecules. On the Cu(111) surface instead, single molecules are found on the terraces, which points to a stronger molecule-substrate interaction.     

4,6‐O‐Benzylidene Directed β‐Mannosylation Without Intermediate Triflate Formation? Comparison of Trichloroacetimidate and DISAL Donors in Microwave‐Promoted Glycosylations under Neutral Conditions

4,6‐Benzylidene‐protected mannosyl donors have emerged as efficient tools for the formation of 1,2‐cis β‐mannosides, which otherwise are difficult to access. Previously studied sulfoxide and trichloroacetimidate mannosyl donors were activated with strong Lewis acids at low temperature and the glycosylations are believed to proceed through intermediate formation of an α‐triflate. This paper describes the synthesis of new benzylidene‐protected glucosyl and mannosyl methyl 3,5‐dinitrosalicylate (DISAL) donors, their application in O‐glycosylations, and comparison with a mannosyl trichloroacetimidate donor. In contrast to previous reports on torsionally “disarmed” donors, these glycosylations were performed in the absence of strong Lewis acids, but in the presence of lithium perchlorate or triflate, using either conventional heating to 40 to 60°C or precise microwave heating to 100 to 150°C. This approach aimed at addressing the question of whether mannosyl triflate intermediates are essential for high β‐selectivity in 4,6‐O‐benzylidene directed mannosylations. We find, again, that precise microwave heating promoted glycosylations under very mild conditions. While a DISAL mannosyl donor gave higher β‐selectivity in the presence of LiOTf than with LiClO₄, the corresponding trichloroacetimidate did not give any β‐selectivity with LiOTf. Thus, under these conditions, the nature of the original leaving group, trichloroacetimidate vs. DISAL, still is important. However, our results point to the possibility of intermediate formation of a mannosyl triflate from a DISAL donor.     

A Benchtop Method for Appending Protic Functional Groups to N‐Heterocyclic Carbene Protected Gold Nanoparticles

The remarkable resilience of N‐heterocyclic carbene (NHC) gold bonds has quickly made NHCs the ligand of choice when functionalizing gold surfaces. Despite rapid progress using deposition from free or CO₂‐protected NHCs, synthetic challenges hinder the functionalization of NHC surfaces with protic functional groups, such as alcohols and amines, particularly on larger nanoparticles. Here, we synthesize NHC‐functionalized gold surfaces from gold(I) NHC complexes and aqueous nanoparticles without the need for additional reagents, enabling otherwise difficult functional groups to be appended to the carbene. The resilience of the NHC?Au bond allows for multi‐step post‐synthetic modification. Beginning with the nitro‐NHC, we form an amine‐NHC terminated surface, which further undergoes amide coupling with carboxylic acids. The simplicity of this approach, its compatibility with aqueous nanoparticle solutions, and its ability to yield protic functionality, greatly expands the potential of NHC‐functionalized noble metal surfaces.